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Perspective on COMMIT/CCS-2 Trial of Clopidogrel in STEMI

Christopher Cannon, M.D. Brigham and Women’s Hospital Boston, MA. Perspective on COMMIT/CCS-2 Trial of Clopidogrel in STEMI. Paradigm of Reperfusion Rx for Acute MI. Thrombolysis. Antithrombotic. Primary PCI. Acute Coronary. Therapy. Occlusion. Recurrent. infarction.

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Perspective on COMMIT/CCS-2 Trial of Clopidogrel in STEMI

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  1. Christopher Cannon, M.D. Brigham and Women’s Hospital Boston, MA Perspective on COMMIT/CCS-2 Trial of Clopidogrel in STEMI

  2. Paradigm of Reperfusion Rx for Acute MI Thrombolysis Antithrombotic Primary PCI Acute Coronary Therapy Occlusion Recurrent infarction Myocardial Necrosis LV Dysfunction Death Braunwald, E. Circulation 1989;79:441-4.

  3. Milestones in the Evolution of Thrombolysis in Myocardial Infarction Mortality 1988 ISIS-2 SK 25% ↓ ASA 23% ↓ 1993 GUSTO-1 TPA 14%↓ 2005 COMMIT/ Clopidogrel 7% ↓ CCS-2

  4. Double-bolus t-PA TNK rPA nPA GP IIb/IIIa inhibition +lytic Oral GP IIb/IIIa Bivalirudin Hirudin Pexulizamab Magnesium Adenosine PSGL GIK etc…. Drugs that Failed to Show Mortality Reduction in STEMI in Past Decade

  5. ST Elevation MI: Clopidogrel Trials COMMIT/CCS-2 46,000 Patients Mortality, D/MI/CVA AMI < 24 hrs Age up to 100 ~50% Lytic No loading dose China Non-invasive Strategy 3,500 Patients Infarct Artery Patency AMI < 12 hrs Age < 75 100% Fibrinolytic Loading dose Europe / N. Amer. Invasive Strategy

  6. Special Considerations for Clinical Use • Bolus vs. no bolus • Benefit on clinical endpoints in both trials emerged in first 24 hrs • CLARITY-TIMI 28: 20% benefit • COMMIT/CCS-2: 9% benefit (~13% in Pts <12 hrs) • Elderly: evidence for benefit in COMMIT • In Pts > 75 years : no loading dose • In Pts < 75 years: 300 mg loading dose • Worldwide public health benefit (1 month <$100 vs. t-PA $2,200) • No excess major bleeding in CABG

  7. Clopidogrel in STEMI • Evidence from 2 large trials in ~ 50,000 patients • Benefit in opening infarct-related artery, and in reducing mortality and morbidity • No excess in major bleeding • Low cost A new addition to treatment of STEMI

  8. Clopidogrel Across Spectrum of CAD UA/NSTEMI PCI Long-term 2o (1o)prevention Acute STEMI CAPRIE Lancet 1996 COMMIT (CCS-2) MI /Stroke/PAD PCI STEMI NSTEMI / UA High-Risk Vascular Disease Up to 3.5 years 1 Year 1 Year 1-3 Years 30 Days + Benefit + Benefit + Benefit (ongoing) + Benefit

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